Extravascular chest wall technetium 99m diethylene triamine penta-acetic acid: implications for the measurement of renal function during renography

Measurement of individual kidney glomerular filtration rate (IKGFR) from the gamma-camera technetium 99m diethylene triamine penta-acetic acid (99mTc-DTPA) renogram requires a continuous measurement of arterial activity. This is usually based on a region of interest (ROI) placed over the cardiac blood pool on the posterior view, with the assumption of negligible contamination from activity in the extravascular space of the chest wall. By injecting a small dose of technetium 99m human serum albumin (HSA) before the 99mTc-DTPA in 12 patients undergoing routine renography, the contribution of extravascular activity to the total signal recorded over the cardiac blood pool was calculated to be 11.0% (SE 2.1%) 1.5 min after DTPA injection, rising to 35.1% (SE 2.5%) at 15 min. Subtraction of the time-activity curve recorded from a ROI of the same size over the right lung generated a "pure" blood signal as shown by almost identical HSA/DTPA signal ratios recorded in blood samples taken 5 min after HSA and 15 min after DTPA and from the gamma-camera at the corresponding times. The effect of using a cardiac blood pool time-activity curve uncorrected for extravascular activity was to overestimate IKGFR by an average factor of 1.17 (SE 0.03).     

Technetium 99m mercaptoacetyltriglycine gamma camera clearance calculations: methodological problems

Major sources of errors in the gamma-camera methods for the calculation of renal clearance are the accuracy of background correction for obtaining the true renal time-activity curve and the validity of the externally recorded pre-cordial activity as an estimate of the plasmatic time-activity curve. With technetium 99m mercaptoacetyltriglycine (^99mTc-MAG3), because of its high protein plasma binding, one could expect minimal extravascular diffusion and hence a more accurate externally detected plasmatic curve. The high extraction rate should reduce the influence of the background, but, on the other hand, the effect of hepatobiliary excretion on the calculation of renal clearance might be significant. Our results suggest that the hepatobiliary excretion of^99mTc-MAG3 does not influence the gamma-camera renal clearance determination, even in patients with low renal function. However, the pre-cordial curve does not reflect accurately the plasmatic disappearance curve; its calibration with a single plasma sample taken at the 20th min is responsible for significant errors, probably because of an unfavourable ratio between the intravascular and extravascular activities at the 20th min. Offprint requests to: M. TondeurParts of this work have been presented at the 17th Annual Meeting of the British Nuclear Medicine Society, London, in April 1989.     

Technetium 99m mercaptoacetyltriglycine gamma camera clearance calculations: methodological problems.

Major sources of errors in the gamma-camera methods for the calculation of renal clearance are the accuracy of background correction for obtaining the true renal time-activity curve and the validity of the externally recorded pre-cordial activity as an estimate of the plasmatic time-activity curve. With technetium 99m mercaptoacetyltriglycine (99mTc-MAG3), because of its high protein plasma binding, one could expect minimal extravascular diffusion and hence a more accurate externally detected plasmatic curve. The high extraction rate should reduce the influence of the background, but, on the other hand, the effect of hepatobiliary excretion on the calculation of renal clearance might be significant. Our results suggest that the hepatobiliary excretion of 99mTc-MAG3 does not influence the gamma-camera renal clearance determination, even in patients with low renal function. However, the pre-cordial curve does not reflect accurately the plasmatic disappearance curve; its calibration with a single plasma sample taken at the 20th min is responsible for significant errors, probably because of an unfavourable ratio between the intravascular and extravascular activities at the 20th min.     

Background in 99Tcm DTPA renography evaluated by the impact of its components on individual kidney glomerular filtration rate

Following injection for renography, 99Tcm-labelled diethylenetriamine-pentacetic acid (DTPA) rapidly enters the extravascular space. Background therefore comprises two components, a falling intravascular signal and an extravascular signal which initially rises. We estimated the relative magnitudes of these two components in terms of their impact on the calculation of differential renal function and individual kidney glomerular filtration rate (IKGFR) from the second phase of the 99Tcm-labelled DTPA renogram in 56 paediatric kidneys. We expressed each of the two background signals as a GFR equivalent. The GFR equivalent of the intravascular signal recorded from a peri-renal background region of interest (ROI), scaled by a factor equal to the ratio of the pixel numbers in the renal and background ROIs, was -39 (S.D. 14) ml min-1. The GFR equivalent of the extravascular signal was smaller than this and opposite to it at 23 (S.D. 10) ml min-1, giving a median ratio for the two equivalents of -1.68. Because of the opposing effects of the two background components on the second phase of the renogram, techniques recently described for the quantification of IKGFR from the renogram, and which eliminate the intravascular component, offer no theoretical advantage over a method of analysis which uses 'direct' subtraction of the total background signal. In practice, however, these new techniques are superior in their handling of 'noisy' data, consistently giving a lower coefficient of variation in their estimation of IKGFR.     

99mTc-DTPA gamma-camera renography: Normal values and rapid determination of single-kidney glomerular filtration rate

A method for ^99mTc-diethylenetriaminepentaacetate (DTPA) gamma-camera renography is presented. From each renogram, an uptake index (UI) proportional to the single-kidney glomerular filtration rate (SKGFR) is defined. If the proportionality factor between UI and SKGFR is the same in all patients, UI can be used as an accurate measure of SKGFR. In order to test this, ^99mTc-DTPA renography was performed in 101 patients with glomerular filtration rates (GFR) varying between 4 and 172 ml/min. The sum of the right-and left-kidney UIs correlated well with the total GFR calculated from the simultaneously measured plasma clearance of ^99mTc-DTPA after a single injection. The correlation coefficient was 0.97. The method was tested in a prospective study of 57 patients. The total GFR estimated from the renograms was not significantly different from the GFR calculated from the plasma clearance of ^99mTc-DTPA. The coefficient of variation—a combination of inaccuracy and imprecision in the estimates as well as in the reference values — was 11.8% at a GFR of 100 ml/min. It is concluded that, in adults, the SKGFR can be calculated as part of the clinical routine from ^99mTc-DTPA gamma-camera renography without determining the injected dose or collecting urine or blood samples. Normal values for some parameters of the renogram obtained in 25 normal subjects are given.     

Visualizing cardiac blood pool: Comparison of three labeling methods

The quality of three different labeling methods of visualizing the cardiac blood pool was investigated in 72 patients:^99mtechnetium labeling of red blood cells in vivo or in vitro and human serum albumin. By the simplified technique of in vitro labeling of RBC from the view point of (1) labeling efficiency, (2) activity in the blood, (3) count rates in a standard ROI over the left ventricle and the paracardiac background, (4) ratio of these count rates, and (5) evaluation of image quality, the best results were obtained. HSA and in vivo labeled RBC led to satisfactory results for visual assessment of ventricular performance in most cases. In spite of the slightly higher technical investment involved in the in vitro labeling method this technique appears to be preferable for gated cardiac blood pool studies in view of the excellent labeling quality.     

The APE nebuliser — a new delivery system for the alveolar targeting of particulate technetium 99m diethylene triamine penta-acetic acid

We report the validation of a new delivery system — aerosol production equipment (known by the acronym APE), which generates a particulate aerosol of technetium 99m diethylene triamine penta-acetic acid (DTPA) with a mass-median aerodynamic diameter of 0.35 m and a geometric standard deviation of 1.8 Twenty subjects were studied; in group 1 were 12 healthy men with normal spirometry; in group 2 were 8 men with AIDS who had mildly abnormal lung function following an episode of pneumocystis pneumonia-spirometry FEV₁ 3.08 (0.73) L, FVC 4.83 (0.82) L [mean (SD)]. The APE nebulizer was used to form a particulate aerosol with 200 MBq of^99mTc DTPA, which was collected in a 351 reservoir of air, which was subsequently inhaled. The mean (SD) inhalation time was 4.7 (0.44) min. The output of the nebulizer (% of activity inhaled) was 82%. Using planar imaging, the penetration index (right lung) in group 1 was 0.93 (0.18), mean (SD), and in group 2 it was 0.91 (0.12). There was virtually no tracheal deposition and extrapulmonary deposition (oropharynx and stomach) was less than 5% of the aerosol delivered. Single-photon emission tomography (SPET) studies carried out in five patients from group 1 confirmed homogeneous intrapulmonary deposition of^99mTc-DTPA. In view of the excellent intrapulmonary deposition of^99mTc-DTPA produced by the APE nebulizer, it may provide an alternative to conventional ventilation studies using radioactive gases.     

Measurement of the ratio of glomerular filtration rate to plasma volume from the technetium-99m diethylene triamine pentaacetic acid renogram: comparison with glomerular filtration rate in relation to extracellular fluid volume

Individual kidney glomerular filtration rate (IKGFR) can be measured from the renogram from the rate of uptake of technetium-99m diethylene triamine penta-acetic acid (^99mTc-DTPA). A blood sample is required to derive IKGFR in millilitres per minute, which is then usually normalised to body surface area. We describe a technique which does not require a blood sample, is already normalised for plasma volume and uses the robust Patlak plot for measuring renal uptake. The rate of kidney uptake, dR(t)ldt, at time = 0, as a fraction of the injected dose, is equal to the fraction of the plasma volume (PV) filtered per minute, i.e. IKGFR/PV. The gradient dR(0)/dt cannot be accurately measured directly but is equal to [ · LV(0)], where is the renal uptake constant (proportional to IKGFR) and LV is the count rate over a left ventricular ROI. LV(0) was obtained by extrapolation of LV(t), while a is the slope of the Patlak plot up to 3 min. GFR/PV (i.e. right plus left kidneys) in patients with normal renal function was about 0.04 min^–1, as would be expected from normal values of GFR (120 ml/min) and plasma volume (3 l). GFR/PV correlated significantly with the ratio of GFR to extracellular fluid volume (ECV), measured from the terminal exponential of the plasma clearance curve (GFR/PV = 3.2.GFR/ECV + 5.3 ml/min/1 [r = 0.82,n = 82]). GFR/PV (r = 0.74) and GFR/ECV (r = 0.82) both correlated inversely and non-linearly with plasma creatinine in 43 studies where the measurement was made within 1 week of the^99mTcDTPA study. They also correlated significantly with the plasma cyclosporin trough level in 14 patients with dermatomyositis on the 30 occasions when this measurement was made within 1 week of the renogram (r = –0.38,P < 0.05 for GFR/PV andr = –0.77,P < 0.001 for GFR/ECV). The ratio of GFR/PV to GFR/ECV is the ratio of extracellular fluid volume to plasma volume, and this was 4.0 (SD 0.99). We conclude that both GFR/PV and GFR/ECV can be easily measured with^99mTc-DTPA and are physiologically valid expressions of GFR. Although GFR/PV and GFR/ECV correlate with each other, the question is raised as to which of the two fluid volumes is the most appropriate for normalising GFR. Correspondence to: A.M. Peters     

Estimation of glomerular filtration rate and technetium-99m diethylene triamine penta-acetic acid using chromium-51 ethylene diamine tetra-acetic acid

Simultaneous measurements of the clearance rate of chromium-51 ethylene diamine tetra-acetic acid (⁵¹Cr-EDTA) and technetium-99m diethylene triamine penta-acetic acid (^99mTc-DTPA) were performed in 54 patients with a range of function between 9 and 176 ml/min. Using multiple blood samples the two clearance values correlated well (r = 0.97, SEE 8.6 ml/min) and DTPA clearance was higher by 2.9%. For each radiopharmaceutical the plasma clearance rates obtained using multiple blood samples were compared with those obtained with simplified methods, i.e., the 60–180 min two-sample method of Russell and the mono-exponential method with the Brochner-Mortensen correction. For both radiopharmaceuticals the clearance values correlated well with the Russell method (r = 0.99, SEE = 4.1 ml/min for EDTA;r = 0.99, SEE 4.9 ml/min for DTPA) and the mono-exponential method (r = 0.99, SEE 3.6 ml/min for EDTA;r = 0.99, SEE 3.9 ml/min for DTPA). The mean plasma clearance obtained using multiple blood samples did not differ significantly from that obtained with the Russell method, either in patients with a glomerular filtration rate (GFR)<30 ml/min or in patients with GFR30 ml/min. The mean plasma clearance obtained using multiple blood samples differed significantly from that obtained with the mono-exponential method because of the great difference observed in patients with GFR30 ml/min. It is concluded that the Russell two-sample method after injection of^99mTc-DTPA is accurate enough for routine clinical use.     

Glomerular filtration rate in relation to extracellular fluid volume: Similarity between99mTc-DTPA and inulin

The rate constant ( ₂) of the terminal exponential of the technetium-99m diethylene triamine pentaacetic acid (DTPA) plasma clearance curve is close to the ratio of glomerular filtration rate (GFR) to extracellular fluid volume (ECV) and is therefore a convenient, already normalised, measure of filtration function. Since ₂ depends on the distribution volume of the tracer, our aim was to compare ₂ from inulin and^99mTc-DTPA and also to compare the equilibration kinetics of the two filtration markers. Fifty millititres of^99mTc-DTPA (250 MBq) and inulin (10%), mixed in the same syringe, were given by intravenous injection in 15 patients undergoing routine^99mTc-DTPA renography for a variety of clinical indications. Frequent antecubital venous blood samples were taken up to about 4 h after injection to construct plasma clearance curves from which GFR, ECV and GFR/ECV (i.e. the reciprocal of mean transit time through the distribution volume) were calculated.^99mTc-DTPA/inulin concentration ratio curves were also constructed after normalisation to the ratio in the syringe. GFR given by the two markers correlated closely (DTPA=0.98·inulin—0.4ml/min;r=0.98).^99mTc-DTPA had the same distribution volume as inulin, had a similar transit time through it and gave the same value of ₂ (r=0.98). GFR/ECV from^99mTc-DTPA accordingly correlated closely with GFR/ECV from inulin (DTPA=0.75·inulin+0.99 ml/min;r=0.95). Even though the distribution volumes and the times to equilibration (i.e. to reach the terminal exponential) were similar, the distribution volume of^99mTc-DTPA at about 10 min after injection was, after subtraction of the plasma volume, about twice that of inulin.We confirm the validity of^99mTc-DTPA for measuring GFR. ₂ is a convenient measure of GFR, can be based on the terminal exponential of inulin of^99mTc-DTPA curves and can be converted to GFR/ECV with an appropriate scaling factor. The kinetics or the two clearance curves with respect to anatomical correlates of the exponentials and the rates of diffusion throughout the respective distribution volumes requires further study.     

Influence of hilar deposition in the evaluation of the alveolar epithelial permeability on <Superscript>99m</Superscript>Tc-DTPA aerosol inhaled scintigraphy

Purpose

We investigated whether hilar radioaerosol deposition affects the clearance rate of technetium-99m-labeled diethylenetriaminepentaacetic acid (^99mTc-DTPA) from peripheral alveolar regions.

Materials and methods

A total of 38 patients underwent ^99mTc-DTPA inhalation lung scintigraphy. Six region of interest (ROI) patterns were adopted: ROI 1 was outlined around the entire hemithorax, and ROIs 2–6 were outlined around the hemithorax but excluded square ROIs of different size in the hilar region. Half-times (T_½) were calculated with time-activity curves using onecompartment and two-compartment analyses. The T_½ of ROIs 1–5 were plotted against the T_½ of ROI 6, and regression lines were obtained with the least-squares method. The absolute values of the differences between surveyed values and regression line were calculated. The Wilcoxon test for trend and a single linear regression model were used to determine statistical significance.

Results

There were significant reductions in the absolute values of the differences between surveyed values and regression line from ROIs 1–5 by one-component analysis and the fast component of two-compartment analysis (P < 0.001).

Conclusion

Our results suggest that the deposition of radioaerosol in the hilar region affects the clearance rate of ^99mTc-DTPA from the alveoli in damaged lungs. The hilar region should be excluded from ROIs when alveolar epithelial permeability is evaluated.

     

Comparison of radionuclide estimation of glomerular filtration rate using technetium 99m diethylenetriaminepentaacetic acid and chromium 51 ethylenediaminetetraacetic acid

Simultaneous measurements of the clearance rates of technetium 99m diethylenetriaminepentaacetic acid (^99mTc-DTPA) and chronium 51 ethylenediaminetetraacetic acid (⁵¹Cr-EDTA) were performed in 30 patients with a range of renal function (glomerular filtration rates between 9 and 120 ml/min). Using multiple blood samples, the two clearance values correlated well (r=0.991, standard error 3.9 ml/min), but DTPA clearance was systematically higher by 7.6%. For each radiopharmaceutical, an equation was derived to correct clearance values obtained using only plasma samples taken at 2 and 4 h for the systematic error inherent in this technique compared with analysis of the complete plasma concentration-time curve. The root mean square error remaining after application of these equations was 1.9 ml/min for both the EDTA and DTPA data. The corresponding errors obtained using the equation derived by Brochner-Mortensen for EDTA plasma clearance were 2.2 ml/min and 1.9 ml/min, respectively, these values were not significantly different from those obtained using the equations derived in this study.     

In vivo labelling of RBC with 99mTc for blood pool imaging using different stannous radiopharmaceuticals

The in vivo ^99mTc-RBC labelling efficiency and stability of labelling was assessed after pretinning with a high-stannous content DTPA kit (Sn DTPA) in comparison with Sn-pyrophosphate (Sn PPi) and a low-stannous DTPA kit (DTPA). The distribution in Sprague Dawley rats showed that similar fractions of administered ^99mTc remained within the blood pool after pretinning with Sn DTPA and Sn PPi when equal quantities of stannous ions (15 g/kg) and equal time intervals (30 min) between successive IV injections of pretinning agent and ^99mTc-pertechnetate were used. Significantly lower fractions were found when DTPA (1.9 g Sn²⁺/kg) was used for pretinning. The rate of ^99mTc elution emphasises the importance of the Sn²⁺ concentration used, not only for labelling efficiency but also for stability of the labelling. Satisfactory intravascular activity, exceeding 80% during the first hour post-injection, was demonstrated in three volunteers after ^99mTc injection, when Sn DTPA was used for pretinning. Left ventricular ejection fractions (LVEF) measured by equilibrium radionuclide angiography angiography after pretinning with Sn DTPA in 24 patients correlated well (r=0.98) with those obtained by contrast angiographies over a broad spectrum of values (0.14–0.72). Four repeated LVEF measurements at 45-min intervals in six additional patients at rest showed excellent reproducibility in each patient: maximum variation was less than 6%.     

Technetium Tc 99m plasmin in the diagnosis of inflammatory disease

The localization characteristics of technetium Tc 99m plasmin were studied in experimental animals to investigate the use of^99mTc-plasmin for imaging inflammatory processes. At various times after abscess induction using turpentine in rats, the in vivo distribution properties of^99mTc-plasmin, gallium citrate Ga 67,¹²⁵I-fibrinogen, and^99mTc-human serum albumin (HSA) were studied by gamma-camera imaging. The in vivo binding of each radiopharmaceutical was also tested in rat and human plasma clots. Region-of-interest analyses of gamma-camera images showed relatively poor^99mTc-plasmin localization at sites of abscess formation. The ratio of abscess-to-control activity of this radiopharmaceutical did not exceed that of⁶⁷Ga,¹²⁵I-fibrinogen, or^99mTc-HSA. In vitro assays of each of the radiopharmaceuticals in plasma clots showed^99mTc-phasmin and¹²⁵I-fibrinogen to have the best localization characteristics.     

<Superscript>99m</Superscript>Tc-DTPA dynamic SPECT and CT volumetry for measuring split renal function in live kidney donors

Objectives  

Split renal function (SRF) estimated from the posterior view of ^99mTc-diethylenetriaminepentaacetic acid planar scintigraphy (DTPA/P) is not sufficiently accurate even after correction for kidney depth by computed tomography (CT). To obtain more accurate SRF using ^99mTc-DTPA, dynamic SPECT method was carried out for the initial 5 min after bolus injection of ^99mTc-DTPA (DTPA/SPECT). Also SRF was evaluated from the renal volume measured by CT. We compared the results with ^99mTc-dimercaptosuccinic acid SPECT (DMSA/SPECT).     

An evaluation of six kits of technetium 99m human serum albumin injection for cardiac blood pool imaging

We have investigated the suitability of five different commercially available kits which provide human serum albumin (HSA) labelled with technetium 99m (^99mTc) for cardiac blood pool imaging. Four of these products were one-step processes using stannous chloride as the reducing agent; the fifth was based on an electrolytic reduction. In addition, we also assessed our own modification of the electrolytic method.We measured the radiochemical purity by precipitation with trichloroacetic acid and by gel filtration on a Biogel P4 column. In addition, we measured the clearance of radioactivity from the blood at frequent time intervals after intravenous injection.Each product was assessed in separate groups of six patients. The labelling efficiency of the one-step kits varied between 73 and 93% compared with 94 and 98% for the electrolytically labelled albumin. The blood clearance for all one-step kits was significantly faster than that obtained for the radiopharmaceuticals prepared by the electrolytic method. We conclude that HSA labelled with^99mTc by the electrolytic method is to be preferred.     

Assessment of alveolar epithelial permeability in Behçet’s disease with <Superscript>99m</Superscript>Tc-DTPA aerosol scintigraphy

Objective

Behçet’s disease (BD) is a multisystem disorder characterized by vasculitis, and consists of a triad of recurrent ulcers of the oral and genital mucosa with relapsing uveitis. The prevalance of pulmonary involvement varies in the range of 1–10% in various studies and its complications are severe and life threatening. In this study, we investigated the changes of pulmonary epithelial permeability of patients with BD using technetium-99m diethylene triamine penta-acetic acid (^99mTc-DTPA) aerosol scintigraphy, so as to begin the therapy regimen as soon as possible.

Methods

Twenty-one nonsmoking patients with BD (8 women, 13 men; mean age 38.67 ± 8.86 years) and 15 healthy volunteer nonsmoking controls (8 women, 7 men; mean age 50.87 ± 12.45 years) underwent ^99mTc-DTPA aerosol inhalation scintigraphy and pulmonary function tests (PFTs). Subjects inhaled 1480 MBq of ^99mTc-DTPA for 4 min in the supine position. Scintigraphic data were recorded dynamically (1 frame/min) in the posterior projection on a 64 × 64 matrix for a 30-min period using a double-headed gamma camera (Infinia, GE, Tirat Hacarmel, Israel) equipped with a low-energy all-purpose parallel hole collimator. Half time of ^99mTc-DTPA clearance (T _1/2) was calculated by placing a mono-exponential fit on the curves. Penetration index (PI) was also calculated by dividing the peripheral total counts by the sum of the peripheral and central total counts on the first minute image, in order to quantify the distribution of the inhaled aerosol.

Results

The clearance half time of ^99mTc-DTPA radioaerosols in the BD patients (24.81 ± 6.22 min) was faster than in the normal control group (46.53 ± 22.41 min) (P = 0.004). There was also a significant difference between PI of the patients with BD (0.15 ± 0.03) and that of the controls (0.21 ± 0.06) (P = 0.002). No correlation was found between the mean T _1/2 values of ^99mTc-DTPA clearance or the spirometric measurements in the BD patients. Penetration indices were not correlated with PFT in the BD patients.

Conclusions

Lung epithelial permeability of the patients with BD was significantly higher than that of the normal subjects. The results of this study demonstrated that the assessment of lung epithelial permeability using ^99mTc-DTPA aerosol scintigraphy could predict the presence of lung involvement in the early stages of BD.

     

Technetium Tc 99m plasmin in the diagnosis of inflammatory disease

The localization characteristics of technetium Tc 99m plasmin were studied in experimental animals to investigate the use of 99mTc-plasmin for imaging inflammatory processes. At various times after abscess induction using turpentine in rats, the in vivo distribution properties of 99mTc-plasmin, gallium citrate Ga 67, 125I-fibrinogen, and 99mTc-human serum albumin (HSA) were studied by gamma-camera imaging. The in vivo binding of each radiopharmaceutical was also tested in rat and human plasma clots. Region-of-interest analyses of gamma-camera images showed relatively poor 99mTc-plasmin localization at sites of abscess formation. The ratio of abscess-to-control activity of this radiopharmaceutical did not exceed that of 67Ga, 125I-fibrinogen, or 99mTc-HSA. In vitro assays of each of the radiopharmaceuticals in plasma clots showed 99mTc-plasmin and 125I-fibrinogen to have the best localization characteristics.     

Determination of glomerular filtration rate (GFR) by analysis of capillary blood after single shot injection of 99mTc-DTPA

^99mTc-DTPA was prepared from a kit produced by the Institute of Atomic Energy, Oslo, Norway. Radiochemical purity as determined with gel chromatography ranged from 98.5–99.7% (n=7). The radiopharmaceutical showed no red cell uptake and not more than 0.2% protein binding in in vitro biokinetic studies.The clearance of ^99mTc-DTPA was compared to the clearance of ¹²⁵I-Iothalamate simultaneously using single shot intravenous injection and biexponential analysis of plasma activity disappearance rate according to Sapirstein et al. (1955). ¹²⁵I-Iothalamate was found to have a higher second volume of distribution than ^99mTc-DTPA, but there was no statistically significant difference in clearance.GFR calculated from capillary serum ^99mTc-DTPA count rates was in all subjects investigated virtually identical with GFR calculated from simultaneously collected venous plasma samples.Estimation of GFR on the basis of plasma activity curves obtained from sampling in two hours gave higher values than estimation from four hours sampling irrespective of kidney function and whether ^99mTc-DTPA or ¹²⁵I-Iothalamate was used.It is concluded that ^99mTc is almost entirely bound to DTPA after intravenous injection of the ^99mTc-DTPA complex, and that the complex is a suitable agent for determination of glomerular filtration rate, using both venous and capillary blood sampling.     

Two routes for 99mTc-DMSA uptake into the renal cortical tubular cell

Critical factors determining the renal handling of ^99mTc-dimercaptosuccinic acid (DMSA) are protein binding in plasma and the renal ^99mTc-DMSA extraction efficiency. Comparison of the count rate over soft tissue with that over the cardiac blood pool about 1 h after injection demonstrated that ^99mTc-DMSA is not exclusively an intravascular label. ^99mTc-DMSA was 76% protein bound in plasma as demonstrated by HPLC and gel filtration. Assuming that the 24% that is not protein bound is filtered at the glomerulus, the renal extraction efficiency of ^99mTc-DMSA by glomerular filtration is about 5%. Since the total renal extraction efficiency was also found to be about 5%, the majority of the activity that becomes fixed in the renal cortex arrives there as a result of filtration followed by tubular reabsorption rather than by direct extraction from peritubular blood. However, discordant changes in DMSA and DTPA uptake induced by captopril in renovascular hypertension (RVH) suggested that a minority of uptake was by direct peritubular extraction.This kinetic model was supported by indirect measurement of protein binding and extraction efficiency based on the kinetics of ^99mTc-DMSA disappearance from plasma and kinetics of uptake in the kidneys. Furthermore, differential functional studies based on ^99mTc-DMSA and ^99mTc-DTPA before and after captopril in patients with RVH due to unilateral renal artery stenosis confirmed filtration followed by tubular reabsorption as the predominant route for DMSA uptake by the kidney.